Appendix 2. CENTRAL and PEDro search strategy

CENTRAL

PEDro

Search terms for Osteoarthritis

#1. (osteoarthritis* OR osteoarthro* OR gonarthriti* OR gonarthro* OR coxarthriti* OR coxarthro* OR arthros* OR arthrot* OR ((knee* OR hip* OR joint*) near/3 (pain* OR ach* OR discomfort*)) OR ((knee* OR hip* OR joint*) near/3 stiff*)) in Clinical Trials #2. MeSH descriptor Osteoarthritis explode all trees

Declaraciones de interés

Fuentes de financiación

Recursos internos

Institute of Social and Preventive Medicine, University or Bern, Switzerland.

Intramural grants

Recursos externos

Swiss National Science Foundation, Switzerland.

National Research Program 53 on musculoskeletal health (grant numbers 4053-40-104762/3 and 3200-066378)

Diferencias entre el protocolo y la revisión

Before embarking on this review, we generated a standard protocol for this and all other Cochrane Reviews performed by our
group. The protocol was approved by the Editorial Board of the Cochrane Musculoskeletal Review Group (CMSG), but, as an update,
did not result in a specific publication in the Cochrane database. We deviated from the standard protocol with respect to
the selection of main outcomes and analysis. The main outcomes specified in the protocol were pain and function, as recommended
for osteoarthritis trials. After approval of the standard protocol, the Editorial Board of CMSG reconvened several times to
establish common views on how to conduct systematic reviews, and it was decided that the main outcomes of future reviews should
reflect both effectiveness and safety. CMSG further agreed to recommend the use of a maximum of two main outcomes. Therefore, the CMSG Editorial Board and
the authors of this review agreed to specify pain intensity and the number of drop-outs or withdrawals due to adverse events
as main outcomes for this update. Function was specified as one of the secondary outcomes. The protocol specified that our
main analysis would be based on standardised mean differences (SMDs) derived from inverse-variance random-effects meta-analysis.
In view of the high degree of heterogeneity, the predominance of small trials of low methodological quality and the skewed
funnel plot for pain intensity as one of the main outcomes, we refrained from presenting the SMD of pain as primary result
in main body of text and summary of findings table, but reported results from uni-variable meta-regression analysis used to
predict treatment effects in trials as large as the largest trials included in the meta-analysis with the standard error as
the explanatory variable. We acknowledge that this analysis is exploratory, however. In addition, we used 'Risk of bias' tables
to present the methodological quality of included trials and a 'Summary of findings' table to present results.

Haddad 2007

Haddad JB,
Obolensky AG,
Shinnick P.
The biologic effects and the therapeutic mechanism of action of electric and electromagnetic field stimulation on bone and
cartilage: new findings and a review of earlier work.
Journal of Alternative and Complementary Medicine (New York, N.Y.) 2007; 13(5): 485-90.

Experimental intervention: TENS and infra-red therapy, 5 times per week Control intervention: sham TENS and infra-red therapy, 5 times per week Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and the intake was assessed

The published report only stated that there was a random allocation of patients to comparison groups. In personal communication,
investigator Serpil Bal stated that the patients were allocated according to last digit of their hospital registration number. Patients
with even numbers were assigned to TENS group, patients with odd numbers to a sham intervention.

Allocation concealment?

No

No, the same investigator responsible of randomisation was giving interventions, as indicated by Serpil Bal in personal communication

Free of selective reporting?

Unclear

Trial protocol not accessible, methods section not explicit about pre-specified outcomes, we have been unable to sort out
this item with investigator Serpil Bal

Adequate blinding of patients?

Yes

Trial is described as single blind study using sham device PlusMED 1-904, indistinguishable from real TENS unit. Sham device
had broken leads, no current passed but flashing light was on. None of the patients had prior experience with TENS.

Extracted pain outcome: global pain after 8 weeks, described as "Intensity of subjective pain sensation (Baseline score on
0-10 cm VAS was standardised to be 100% in each of the groups. Follow up values were expressed as mean decrease in % from
baseline)". No function outcome reported

Comparison 1: 16 out of 16 (100%) randomised to experimental and 16 out of 18 (89%) randomised to control group were analysed
Comparison 2: 15 out of 17 (88%) randomised to experimental and 15 out of 15 (100%) randomised to control group were analysed

Experimental intervention: 20 min TENS in group 1, 40 min TENS in group 2, 60 min TENS in group 4, 5 times per week Control intervention: sham TENS, 5 times per week Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and whether intake was similar between groups

Experimental intervention: noxious adjusted interferential current stimulation in group 1, noxious unadjusted interferential
current stimulation in group 2, innocuous adjusted interferential current stimulation in group 3, innocuous unadjusted interferential
current stimulation in group 4, 3 times per week Control intervention: sham interferential current stimulation, 3 times per week Duration of treatment period: 4 weeks Analgesics allowed, unclear whether intake was similar between groups.

Experimental intervention: burst TENS, twice per day Control intervention: sham TENS, twice per day Duration of treatment period: 6 weeks Analgesics allowed, but change of dosage prohibited. Unclear whether analgesics were assessed and whether intake was similar
between groups.

Use of sham device: Codetron, identical in appearance, set at frequency of 0.2 Hz with a threshold electrical stimulus of
0.5 mA, which caused a sensation on the skin but failed causing the deep muscle afferent stimulation

*Due to major protocol violations, all 42 randomised patient of one site were excluded by Garland et al

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Random number table

Allocation concealment?

Yes

Central randomisation

Free of selective reporting?

Unclear

Quote: "Total WOMAC scores were not a defined outcome in the protocol, but are shown in Tables II(a)-(d)."

Adequate blinding of patients?

Yes

Use of sham device: BIO-1000, indistinguishable from active device, with automatic shut-off as soon as amplitude is reduced
(all patients were instructed to reduce intensity just below perception level). Further adjustments required all devices to
be restarted.

Experimental intervention: high frequency TENS, once only in group 1, burst TENS, once only in group 2 Control intervention: sham TENS, once only Duration of treatment period: 1 day Analgesics not allowed

Experimental intervention: 2 Hz TENS in group 1, 100 Hz TENS in group 2, modulation TENS with alternations between 2 to 100
Hz in group 3, 5 times per week in all groups Control intervention: sham TENS, 5 times per week Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and whether intake was similar between groups

Extracted pain outcome: pain on walking after 4 weeks, described as "intensity of pain felt while walking (VAS)" No function outcome reported

No primary outcome reported

Notes

Outcome data were reported on knee level.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "Randomization was carried out by drawing lots from the randomization envelope."

Allocation concealment?

Unclear

No information provided

Free of selective reporting?

Unclear

Insufficient information provided; no access to study protocol

Adequate blinding of patients?

Yes

Use of sham device: identical in appearance, internal circuit disconnected, no current passed, indicator light on, digital
display of intensity control functioned normally. Quote: "Only therapists who administered treatment to the subjects knew
the group allocation, while the subjects and the assessor were not given this information."

Experimental intervention: TENS, 5 times per week Control intervention: sham TENS, 5 times per week Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and whether intake was similar between groups

**Only baseline values reported in the report. Contact established with investigators Law and Cheing, who provided end of
treatment and follow-up data.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "'by drawing lots from the randomization envelope without replacement"

Allocation concealment?

Unclear

Quote : "(...) carried out by physiotherapists who performed the treatment"

Free of selective reporting?

No

No results reported for some outcomes mentioned in the methods section, including pain intensity on VAS

Adequate blinding of patients?

Yes

Use of sham device: ITO model 120Z, no current delivered but flashing light on. Quote: "The assessors and subjects were blind
to the group allocation. All subjects were told that when the indicator light of the TENS was blinking, it meant the machine
was working properly. They might or might not feel any tingling sensation during treatment because the intensity of the current
was small."

Experimental intervention: TENS, 4 times per week, with a total of 8 applications and educational pamphlet Control intervention: educational pamphlet Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and whether intake was similar between groups

Extracted pain outcome: other after 26 weeks, described as "Pain composite score with items rest, post-exercise and night
pain (approach unclear; either VAS or verbal scoring technique modified after Newland)"** Extracted function outcome: other algofunctional scale after 26 weeks, described as "Overall clinical condition scale developed
by authors, which was based on 3 items for pain; rest-, post-exercise-, night pain and 3 for function; gait, method of climbing
stairs and using walking aids (most likely Likert)".

No primary outcome reported

Notes

*1 trial arm, in which shortwave diathermy was given, was excluded, **only baseline values with standard error and P values
for change from baseline per group reported. No contact could be established with the investigators.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

No information provided

Allocation concealment?

Unclear

No information provided

Free of selective reporting?

No

No results reported for some outcomes mentioned in the methods section, including maximum knee girth

Experimental intervention: TENS, twice per week* Control intervention: sham TENS, twice per week* Duration of treatment period: 4 weeks Analgesics intake assessed and found to be similar between groups

Sealed assignment envelopes, but unclear whether these were opaque and sequential

Free of selective reporting?

No

No results reported for some outcomes mentioned in the methods section, including sleep disturbance

Adequate blinding of patients?

Yes

Use of sham device: RDG Tiger Pulse with broken electrode connection at jack point, no current passed but flashing light on.
Quote: "Exactly the same procedure were followed for both the treatment and control groups".

100 patients randomised, 25 per group 100 patients with knee OA reported at baseline Study joints: 100 knees Number of females: 91 of 100 (91%) Average age: 58 years

Interventions

Experimental intervention: TENS, 5 times per week Control intervention: sham TENS, 5 times per week Duration of treatment period: 2 weeks Unclear whether analgesics were allowed and whether intake was similar between groups

Sham device: MEA-TENS with broken lead at jack plug, no current passed but red indicator light on. Quote: "(...) treatment
appeared to be done in the same way as the other groups without the subjects suspecting the nature of the stimulation".

Investigators reported that "no subject was withdrawn either active or placebo groups". However, the reported degrees of freedom
indicate that 5 out of 100 patients were not included. It remained unclear to which of the 4 groups the excluded patients
belonged.

Extracted pain outcome: global pain after 34 weeks described as "Patient evaluation of pain of treated knee (Baseline based
on 0-10 VAS, follow-up based on % change from baseline)" Extracted function outcome: patient's global assessment after 34 weeks, described as "Patient evaluation of function of treated
knee (Baseline based on 0-10 VAS, follow-up based on % change from baseline)"

TENS as part of a combined experimental intervention. Additional description design: 3 groups, Group A receiving auricular
acupuncture, diet control and aerobic exercise, Group B like A with addition of TENS and ultrasound, Group C receiving TENS
and ultrasound; unclear whether allocation was at random.

Cross-over RCT reporting pooled results after completion of all phases. Contact established with Daniel and Beverly Lewis,
who were unable to provide results for the first phase (before cross-over)

Lewis 1985

RCT reporting P values of effect only. Contact established with Daniel and Beverly Lewis, who could not provide any additional
outcome data, nor could they indicate whether the design concerned a cross-over or a parallel RCT

Lewis 1988

Published abstract addressing the same cross-over RCT reported by Lewis 1994

Lewis 1994

Cross-over RCT reporting pooled results after completion of all phases. Contact established with Daniel and Beverly Lewis,
who were unable to provide results for the first phase (before cross-over)

Lone 2003

Not a randomised controlled study. Additional description: before-after study design that was incorrectly labelled as randomised
study by original authors.

Lund 2005

Not concerning osteoarthritis

Macchione 1995

Not a randomised controlled trial (review)

Matti 1987

Not concerning osteoarthritis, not a randomised clinical trial. Tetanus-like faradisation electrostimulation with exercise
after surgical removal of meniscus, primarily aiming at muscle enhancement. Active control with 10 Hz sinusoidal current application
and exercise.

Mixed population, only 4 out of 163 patients reported to have knee, hip or ankle OA

Paillard 2005

Not concerning osteoarthritis (healthy volunteers)

Picaza 1975

Not concerning osteoarthritis and not a randomised controlled trial

Salaj 2001

Not a randomised controlled trial, combined multiple interventions in both interventions and control group

Salim 1996

Not a randomised controlled trial (review)

Sluka 1998

Animal study

Sok 2007

Concerns chronic knee pain. First author was contacted by email to verify how many patients had osteoarthritis. No response
received. Additional description: article in Korean, using a TENS device, abstract however suggests that parameters were set
to strengthen muscles.

Svarcova 1988a

Use of active control groups. Additional description: controlled trial with groups receiving either galvanic electrostimulation
or YES ultrasound or pulsed shortwaves. Within these groups, half of the patients received ibuprofen, half received placebo
ibuprofen. It was unclear whether allocation was at random.

Svarcova 1988b

See Svarcova 1988a. Double publication of the same study, including the same number of patient and outcome data.

Incomplete presentation of data. Additional description: cross-over randomised clinical trial presenting pooled results only.
Contact established with Mark Hallett, who was unable to provide data concerning the first phase, before cross-over. We were
unable to contact the other authors.

Tulgar 1991

Not concerning osteoarthritis

Volklein 1990

Use of active control group. Additional description: random allocation of patients to 4 different types of diadynamic current.

Weiner 2007

Not transcutaneous but periosteal (needle) application

Zivkovic 2005

Use of active control group. Additional description: the combination of low-energy laser, pulsed electromagnetic field and
kinesitherapy was compared to the combination of electrotherapy, pulsed electromagnetic field and kinesitherapy.

Randomisation method: not reported Concealment of allocation: not reported

Blinding: not reported

Sample size calculation: not reported

Analyses: not reported whether is based on intention-to-treat principle

Trial duration: 6 weeks

Sponsored by: not reported

Participants

261 (87 in each arm) patients with primary knee OA to be randomised Study joints: knees Selection criteria: knee pain, radiographic (X-ray) evidence of osteophytes, and at least 1 of the following 3 criteria: 50
years or older, morning stiffness that lasts for less than 30 minutes, crepitus on active movement

Interventions

Experimental intervention: TENS, as much as needed and group education including self-efficacy and exercise training, once
per week Control intervention 1: Sham TENS, as much as needed and group education once per week, as described above Control intervention 2: group education once per week, as described above Duration of treatment period: 6 weeks Analgesics: unclear wether analgesic intake is allowed and is measured

Device: not reported Self-administered: yes Waveform: not reported Pulse width: not reported Pulse frequency: not reported Amplitude: "strong but comfortable" tingling sensation Duration of stimulation: defined as "as much as needed" Electrodes: not reported Electrode placement: within or close to the site of pain

Sham device: identical in appearance, displays are active but there is no current output

The estimated pain in the intervention group of large trials was derived from meta-regression using the standard error as
independent variable

Function

Various validated function scales

Median follow-up: 4 weeks

-1.2 units on WOMAC(range 0 to 10)1

21% improvement

-2.3 units on WOMAC(Δ -1.1, -1.6 to -0.6)5

41% improvement (Δ +20%, +11% to +29%)6

SMD -0.34 (-0.54 to -0.14)

407 (9 studies)

+OOO very low7

NNT: 29 (95% CI 19 to 69)8

Number of patients experiencing any adverse event

Median follow-up: 4 weeks

150 per 1000 patient-years1

153 per 1000 patient-years (80 to 296)

RR 1.02 (0.53 to 1.97)

175 (3 studies)

++OO low9

No evidence of harmful effect

(NNH: not statistically significant)

Number of patients withdrawn or dropped out because of adverse events

Median follow-up: 4 weeks

17 per 1000 patient-years1

16 per 1000 patient-years (3 to 102)

RR 0.97 (0.16 to 6.00)

363 (8 studies)

+++O moderate10

No evidence of harmful effect

(NNH: not statistically significant)

Number of patients experiencing any serious adverse event

Median follow -up: 4 weeks

4 per 1000 patient-years1

1 per 1000 patient-years (0 to 29)

RR 0.33 (0.02 to 7.32)

195 (4 studies)

++OO low11

No evidence of harmful effect

(NNH: not statistically significant)

*The basis for the assumed risk in the safety outcomes (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

GRADE Working Group grades of evidence High quality (++++): Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (++OO): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to
change the estimate. Very low quality (+OOO): We are very uncertain about the estimate.

1 Median reduction as observed across control groups in large osteoarthritis trials (Nuesch 2009). 2 Standardised mean differences (SMDs) were back-transformed onto a 10 cm visual analogue scale (VAS) on the basis of a typical
pooled SD of 2.5 cm in trials that assessed pain using a VAS, and expressed as change based on an assumed standardised reduction of 0.72 standard deviation units in the
control group. 3 The median observed pain score at baseline across control groups in large osteoarthritis trials was 6.1 cm on a 10 cm VAS
(Nuesch 2009). 4 Downgraded (3 levels) because the effect was estimated from a meta-regression model using the standard error as independent
variable and because included trials were generally of low quality and small sample size: only 2 out of 16 trials used adequate
concealment of allocation, only 3 performed analyses according to the intention-to-treat principle, and the presence of large
between trial heterogeneity. 5 Standardised mean differences (SMDs) were back-transformed onto a 0 to 10 standardised WOMAC function score on the basis
of a typical pooled SD of 2.1 in trials that assessed function on WOMAC function scale and expressed as change based on an assumed standardised reduction of 0.58 standard
deviation units in the control group. 6 The median observed standardised WOMAC function score at baseline across control groups in large osteoarthritis trials was
5.6 units (Nuesch 2009). 7 Downgraded (3 levels) because included trials were generally of low quality and small sample size: 1 out of 9 studies used
adequate concealment of allocation methods, only 2 performed analyses according to the intention-to-treat principle, presence
of moderate between trial heterogeneity, 9 out of 18 studies reported this outcome, likely leading to selective outcome reporting
bias. 8 Absolute response risks for function in the control groups were assumed 26% (see Methods section). 9 Downgraded (2 levels) because the confidence interval crosses no difference in the pooled estimate, 1 out of 3 studies included
all patients in this analysis, 3 out of 18 studies reported this outcome, likely leading to selective outcome reporting bias.
10 Downgraded (1 level) because the confidence interval of the pooled estimate is wide and crossed no difference, 8 out of 18
studies reported this outcome, possibly leading to selective outcome reporting bias. 11 Downgraded (2 levels) because 4 out of 18 studies reported this outcome, possibly leading to selective outcome reporting
bias, the confidence interval of the pooled estimate is wide and crossed no difference.

Table 1. Results of stratified analyses of pain outcomes

Variable

N of trials

N of patients (experimental)

N of patients (control)

Pain intensity

Heterogeneity

P for interaction

n

n

n

SMD (95% CI)

I2 (%)

All trials

16

440

286

-0.86 (-1.23 to -0.49)

80%

Allocation concealment

0.47

Adequate

2

79

39

-0.52 (-0.91 to -0.13)

0%

Inadequate or unclear

14

361

247

-1.03 (-1.49 to -0.57)

84%

Type of control intervention*

0.12

Sham intervention

12

354

216

-1.13 (-1.59 to -0.67)

82%

No control intervention

5

86

70

-0.31 (-0.80 to 0.19)

58%

Blinding of patients

0.37

Adequate

11

309

205

-1.05 (-1.52 to -0.59)

82%

Inadequate or unclear

6

131

79

-0.63 (-1.31 to 0.05)

81%

Use of analgesic cointerventions

0.36

Similar between groups

4

124

83

-0.57 (-1.16 to 0.02)

74%

Not similar or unclear

12

316

23

-1.10 (-1.60 to -0.59)

84%

Intention-to-treat analysis

0.73

Yes

3

83

63

-0.76 (-1.43 to -0.09)

72%

No or unclear

13

357

223

-1.00 (-1.48 to -0.53)

84%

Type of ES**

0.94

High frequency TENS

8

177

139

-0.82 (-1.51 to -0.12)

86%

Burst TENS

2

39

38

-0.85 (-1.32 to -0.38)

0%

Modulation TENS

1

13

3

-1.41 (-2.92 to 0.10)

N/A

Low frequency TENS

3

46

40

-0.82 (-1.29 to -0.34)

0%

Interferential current stimulation

4

88

44

-1.20 (-1.99 to -0.42)

71%

Pulsed ES

2

77

52

-0.41 (-0.77 to -0.05)

0%

Duration of ES per session†

0.69‡

≤ 20 minutes

8

166

112

-0.95 (-1.55 to -0.35)

78%

30 to 40 minutes

6

156

99

-1.45 (-2.28 to -0.62)

85%

≥ 60 minutes

4

118

91

-0.47 (-0.96 to 0.02)

58%

Number of sessions per week

0.90‡

≤ 3

6

163

91

-0.81 (-1.48 to -0.14)

82%

4 to 6

7

182

125

-1.33 (-2.11 to -0.54)

88%

≥ 7

3

96

70

-0.51 (-0.83 to -0.19)

0%

Duration of ES per week***

0.74‡

≤1 hour

5

123

71

-0.85 (-1.72 to 0.01)

86%

> 1 to 5 hours

8

180

122

-1.42 (-2.11 to -0.74)

81%

> 5 hours

5

137

109

-0.53 (-0.96 to -0.11)

55%

Duration of treatment period

0.14

< 4 weeks

7

190

114

-1.39 (-2.13 to -0.66)

86%

≥ 4 weeks

9

250

172

-0.64 (-1.06 to -0.22)

75%

ES: electrostimulation; *In Cheing 2002, two independent comparisons contributed in the two different strata. **Adedoyin 2005, Grimmer 1992 and Law 2004 contributed to two, two and three different strata: high-frequency TENS and interferential current stimulation, high-frequency
TENS and burst, and high-, low-frequency and modulation TENS, respectively. † = Cheing 2003 contributed to all three different strata, with the same 8 control patients displayed in each stratum. ‡ = P values from
test for trend.

Table 2. Results of stratified analyses of function

Variable

N of trials

N of patients (experimental)

N of patients (control)

Function

Heterogeneity

P for interaction

SMD (95% CI)

I2 (%)

All trials

9

226

181

-0.34 (-0.54 to -0.14)

0%

Allocation concealment

0.88

Adequate

1

39

19

-0.29 (-0.85 to 0.26)

N/A

Inadequate or unclear

8

187

162

-0.34 (-0.56 to -0.12)

5%

Type of control intervention

0.14

Sham intervention

5

151

120

-0.46 (-0.70 to -0.21)

0%

No control intervention

4

75

61

-0.10 (-0.45 to 0.24)

0%

Blinding of patients

0.14

Adequate

5

151

120

-0.46 (-0.70 to -0.21)

0%

Inadequate or unclear

4

75

61

-0.10 (-0.45 to 0.24)

0%

Use of analgesic cointerventions

0.95

Similar between groups

2

69

48

-0.33 (-0.70 to 0.05)

0%

Not similar or unclear

7

157

133

-0.34 (-0.60 to -0.08)

15%

Intention-to-treat analysis

0.76

Yes

2

40

42

-0.28 (-0.71 to 0.16)

0%

No or unclear

7

186

139

-0.35 (-0.58 to -0.12)

5%

Type of ES**

0.32

High frequency TENS

4

84

70

-0.18 (-0.50 to 0.14)

0%

Burst TENS

0

Modulation TENS

0

Low frequency TENS

1

25

25

-0.88 (-1.46 to -0.30)

N/A

Interferential current stimulation

3

40

34

-0.27 (-0.75 to 0.20)

0%

Pulsed ES

2

77

52

-0.36 (-0.72 to -0.00)

0%

Duration of ES per session

0.80‡

≤ 20 minutes

5

100

86

-0.29 (-0.69 to 0.11)

44%

30 to 40 minutes

2

49

43

-0.37 (-0.79 to 0.04)

0%

≥ 60 minutes

2

77

52

-0.36 (-0.72 to -0.00)

0%

Number of sessions per week

0.32‡

≤ 3

4

75

61

-0.10 (-0.45 to 0.24)

0%

4 to 6

3

74

68

-0.54 (-0.88 to -0.20)

2%

≥ 7

2

77

52

-0.36 (-0.72 to -0.00)

0%

Duration of ES per week

0.32‡

≤ 1 hour

4

75

61

-0.10 (-0.45 to 0.24)

0%

> 1 to 5 hours

3

74

68

-0.54 (-0.88 to -0.20)

2%

> 5 hours

2

77

52

-0.36 (-0.72 to -0.00)

0%

Duration of treatment period

0.18

< 4 weeks

3

74

68

-0.54 (-0.88 to -0.20)

2%

≥ 4 weeks

6

152

113

-0.23 (-0.47 to 0.02)

0%

ES: electrostimulation; **Adedoyin 2005 contributed to two different strata: high-frequency TENS and interferential current stimulation; ‡ = P values from test for
trend.

Figuras

Figure 1

Flow chart

Figure 2

Methodological characteristics and source of funding of included trials. (+) indicates low risk of bias, (?) unclear and (-)
a high risk of bias on a specific item.

Figure 3

Forest plot of 16 trials comparing the effects of any type of transcutaneous electrostimulation and control (sham or no intervention)
on knee pain. Values on x-axis denote standardised mean differences. The plot is stratified according to type of electrostimulation.
Law 2004 reported on knee level, we inflated the standard error with sqrt(number knees)/sqrt(number patients) to correct for clustering
of knees within patients. Adedoyin 2005 and Cheing 2002 contributed with two comparisons each. In Adedoyin 2005, the standard error was inflated and the number of patients in the control group was halved to avoid duplicate counting of
patients when including 2 both comparisons in the overall meta-analysis. Data relating to the 3, 2, 3 and 4 active intervention
arms in Cheing 2003, Grimmer 1992, Law 2004 and Defrin 2005, respectively, were pooled.

Figure 4

Funnel plot for effects on knee pain. Numbers on x-axis refer to standardised mean differences (SMDs), on y-axis to standard errors of SMDs.

Figure 5

Forest plot of 8 trials comparing patients withdrawn or dropped out because of adverse events between any transcutaneous electrostimulation
and control (sham or no intervention). Values on x-axis denote risk ratios. Risk ratios could not be estimated in 5 trials,
because no drop-out occurred in either group. The plot is stratified according to type of electrostimulation. Data relating
to the 3 and 2 active intervention arms in Cheing 2003 and Grimmer 1992, respectively, were pooled.

Figure 6

Forest plot of 9 trials comparing the effects of any type of transcutaneous electrostimulation and control (sham or no intervention)
on function. Values on x-axis denote standardised mean differences. The plot is stratified according to type of electrostimulation.
In Adedoyin 2005, the standard error was inflated and the number of patients in the control group was halved to avoid duplicate counting of
patients when including both comparisons in the overall meta-analysis.

Figure 7

Funnel plot for effects on functioning of the knee. Numbers on x-axis refer to standardised mean differences (SMDs), on y-axis to standard errors of SMDs.

Figure 8

Forest plot of 3 trials comparing patients experiencing any adverse event between any transcutaneous electrostimulation and
control (sham or no intervention). Values on x-axis denote risks ratios. The risk ratio in one TENS trial could not be estimated
because no adverse event occurred in either group. The plot is stratified according to type of electrostimulation.

Figure 9

Forest plot of 4 trials comparing patients experiencing any serious adverse event between any transcutaneous electrostimulation
and control (sham or no intervention). Values on x-axis denote risk ratios. Risk ratios could not be estimated in 3 trials,
because no serious adverse event occurred in either group. The plot is stratified according to type of electrostimulation.
Data relating to the 3 active intervention arms in Cheing 2003 were pooled.